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PMID: 19696022 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CD38/cADPR/Ca2+ pathway promotes cell proliferation and delays nerve growth factor-induced differentiation in PC12 cells.

The Journal of biological chemistry ·Vol. 284 ·No. 43 ·2009-10-23 ·Pages 29335-42

Yue J, Wei W, Lam CM, Zhao YJ, Dong M, Zhang LR, Zhang LH, Lee HC

Abstract

Intracellular Ca(2+) mobilization plays an important role in a wide variety of cellular processes, and multiple second messengers are responsible for mediating intracellular Ca(2+) changes. Here we explored the role of one endogenous Ca(2+)-mobilizing nucleotide, cyclic adenosine diphosphoribose (cADPR), in the proliferation and differentiation of neurosecretory PC12 cells. We found that cADPR induced Ca(2+) release in PC12 cells and that CD38 is the main ADP-ribosyl cyclase responsible for the acetylcholine (ACh)-induced cADPR production in PC12 cells. In addition, the CD38/cADPR signaling pathway is shown to be required for the ACh-induced Ca(2+) increase and cell proliferation. Inhibition of the pathway, on the other hand, accelerated nerve growth factor (NGF)-induced neuronal differentiation in PC12 cells. Conversely, overexpression of CD38 increased cell proliferation but delayed NGF-induced differentiation. Our data indicate that cADPR plays a dichotomic role in regulating proliferation and neuronal differentiation of PC12 cells.

MeSH Terms
ADP-ribosyl Cyclase/biosynthesis,genetics ADP-ribosyl Cyclase 1/biosynthesis,genetics Acetylcholine/metabolism,pharmacology Animals Calcium/metabolism Calcium Signaling/physiology Cell Differentiation/drug effects,physiology Cholinergic Agents/metabolism,pharmacology Cyclic ADP-Ribose/genetics,metabolism Membrane Glycoproteins/biosynthesis,genetics Nerve Growth Factor/genetics,metabolism,pharmacology Neurons/cytology,metabolism PC12 Cells Rats
Chemicals
Cholinergic Agents Membrane Glycoproteins Cyclic ADP-Ribose Nerve Growth Factor ADP-ribosyl Cyclase Cd38 protein, rat ADP-ribosyl Cyclase 1 Acetylcholine Calcium
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Yue Jianbo
Department of Physiology, The University of Hong Kong, Hong Kong. [email protected]
Wei Wenjie
Lam Connie M C
Zhao Yong-Juan
Dong Min
Zhang Liang-Ren
Zhang Li-He
Lee Hon-Cheung
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M109.049767
Email
[email protected]
Published
2009-10-23
Epub
2009-00-20
Pages
29335-42
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2785564
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M109.049767 PMC Full Text View journal details
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